The Postmenopausal Estrogen/Progestins Intervention (PEPI-1) trial of 875 participants followed at 7 centers for three years is the largest and longest randomized double-blind placebo-controlled clinical trial of hormone treatment in postmenopausal women -- and the only long-term trial of estrogen-progestin regimens. It is the only long-term trial designed to compare the effects of Estrogen Replacement Therapy (ERT) and combined (Estrogen-progestin) hormone replacement therapy (HRT) on heart disease risk factors. It is also unique for the number of women who began ERT or HRT more than 5 years after the menopause. Details of the study design, hormone replacement regimens and study populations are given in Project I, as are the major analyses of PEPI-1 data proposed for completion during the extended follow-up period. Project II, Studies of Repository Samples, was planned to utilize plasma, urine and other samples already collected but not analyzed by the close of PEPI-1. Both Project I and Project II, submitted by the Coordinating Center to reflect the centralized activity necessary for a multicenter project, will be conducted with the Clinical Investigators as a cooperative project. Project III, submitted in parallel from each of the 7 PEPI Clinical Centers, describes a three year prospective observational follow-up study designed to: ensure PEPI women's safety and learn more about possible delayed adverse hormone effects; study treatment choices, compliance and reasons related to these decisions; and monitor long-term effects on heart disease risk factors and bone density. All participants will be invited to an annual clinic visit, (conducted according to the established PEPI-1 protocol) which includes a medical history and limited examination, mammogram, endometrial biopsy, and standardized questions about quality of life, sexuality, symptomatology, and medication use. We will measure primary PEPI endpoints (HDL-cholesterol, blood pressure, insulin and fibrinogen and their covariates, and bone density at the hip and spine.